RV1 Colgate 2016‐BGD

Methods	RCT, open‐label non‐placebo controlled trial Length of follow‐up: outcomes measured at 1 year Adverse event data collection methods: Passive: All adverse events following interventions were captured for 48 hours following each intervention and were scored for probable, possible, or unlikely relationship to each intervention. All missing protocol‐defined events were captured as protocol deviations and reported annually. Comprehensive safety reports were submitted semi‐annually to the study’s Independent Medical Monitor and to the Data and Safety Monitoring Board
Participants	Number: 700 enrolled; 593 evaluable Age range: birth to age 7 days at enrolment, 10 ‐ 17 weeks at vaccine administration Inclusion criteria: Healthy infant aged 0 to 7 days, no obvious congenital abnormalities or birth defects, no abnormal (frequency and consistency) stools since birth, stable household with no plans to leave the area for the next one year Exclusion criteria: Parents are not willing to have child vaccinated at the field clinic or to have child's blood drawn, parents are planning to enrol child into another clinical study, mother not willing to have blood drawn and breast milk extracted, parents not willing to have field research assistant in home twice a week, history of seizures or other apparent neurologic disorders, infant received any vaccines before start of study, except Bacillus Calmette‐Guerin (BCG), infant has any sibling currently or previously enrolled in this study (including a twin)
Interventions	1. RV1 dose 1 at 10 weeks, dose 2 at 17 weeks (350 enrolled participants) 2. No RV1 vaccine (350 enrolled participants)
Outcomes	Clinical outcome measures (safety and efficacy) 1. Rotavirus diarrhoea (severe) 2. All‐cause diarrhoea (severe) 3. All‐cause deaths 4. Rotavirus diarrhoea (any severity) 5. All‐cause diarrhoea (any severity) 6. Dropouts from the trial
Immunization status	Along with Rotarix at 10 and 17 weeks of age, the polio vaccine intervention was the administration of an injected, inactivated polio vaccine (IPV) dose replacing the fourth dose of tOPV at 39 weeks of age. In addition to the vaccine interventions, study children received all standard EPI vaccines through the study clinic.The national Bangladesh Expanded Program on Immunizations (EPI) schedule includes BCG at birth; pentavalent vaccine (DPT, HepB, Hib) at 6, 10, and 14 weeks; bivalent Measles‐Rubella at 40 weeks; and monovalent Measles at 65 weeks
Location	Single site, Bangladesh WHO mortality stratum D
Notes	Date: May 2011 to November 2013 Source of funding: Bill and Melinda Gates Foundation Study rationale: The primary objective was to determine the efficacy of a 2‐dose Rotarix oral rotavirus vaccine (given at 10 and 17 weeks of age) to prevent rotavirus diarrhoea in the first year of life
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomized using permuted blocks with random block size selection.
Allocation concealment (selection bias)	Low risk	All clinical investigators and laboratories were masked to vaccine arm, but medical officers were not.
Blinding (performance bias and detection bias) All outcomes	High risk	RV1 versus no intervention, unable to blind (no placebo)
Incomplete outcome data (attrition bias) All outcomes	Low risk	Primary ITT analysis, moderate attrition.
Selective reporting (reporting bias)	Low risk	All relevant outcomes appear to be reported, protocol published
Other bias	Low risk	No other bias apparent